Hepatoblastoma (HB) is a rare liver tumor, the incidence rate of which doubled between 1975 and 1999 in the U.S. Recent evidence suggests increased risk of HB in low (LBW: 1,500-2,500 grams), and especially very low (VLBW: <1,500 grams) birth weight infants. Small (<100 cases) casecontrol studies have also suggested associations of HB with maternal smoking while pregnant,parental occupation, and a polymorphism in the myeloperoxidase (MPO) gene. We propose to conduct the largest and most comprehensive case-control study of hepatoblastoma to date. We will collect 600 cases of HB diagnosed at U.S, Children's Oncology Group institutions in 2000-2008,about 120 of whom should be LBW and VLBW. Controls (480 normal birth weight;120 LBW;120 VLBW) will be selected from United States birth registries and will be frequency matched on birth weight, sex, year of birth, and region of diagnosis. Exposure data will be collected through parental interview and buccal cells will be collected for DNA analysis;cases will also have their tumor tissue collected. Our primary aims are to: 1) Determine whether duration and intensity of treatment for prematurity increases risk of HB among LBW and VLBW infants, 2) Examine the role of parental occupation and maternal lifestyle while pregnant in the risk of HB, 3) Compare the frequency of candidate genetic susceptibility gene polymorphisms in cases and controls, 4) Compare the frequency of candidate genetic susceptibility gene polymorphisms in the mothers of cases and controls, 5) Describe the pattern of IGF-2 gene imprinting in HB cases in toto, by age, and by birthweight. We hypothesize that treatment for prematurity is the major risk factor among low birth weight children and that the other exogenous exposures are of minor etiologic importance. We further hypothesize that endogenous determinants of the ability to activate and detoxify toxins are risk factors among children with both normal and low birth weight.